"Wide swaths of people benefit from statins and we need to consider both their effects on the lipids as well as these novel pleiotropic effects, including those on systemic inflammation," said Michael Blaha, MD, MPH.

New data showing that high-dose atorvastatin can reduce periodontal inflammation in as little as four weeks suggests a new mechanism of action for statins. In addition to the familiar reduction in low-density lipoprotein cholesterol (LDL-C), reductions in systemic inflammation and reduction in inflammatory activity within atherosclerotic plaques, statins may also reduce non-arterial inflammation in tissues such as the periodontium. This reduction in local tissue inflammation may lead to a reduction in pro-inflammatory mediators released into systemic circulation, which in turn may lead to reductions in atherosclerotic inflammation, according to a study published Oct. 2 in the Journal of the American College of Cardiology.

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Researchers compared the effect of a daily atorvastatin 80 mg dose versus a 10 mg dose in a randomized, multi-center trial with 71 subjects with established atherosclerosis or risk factors for atherosclerosis. Patients were evaluated using F-Flurodexoyglucose positron emission tomography (FDG-PET) imaging. After 12 weeks, there was a significant reduction in periodontal inflammation in subjects randomized to the 80 mg dose (p=0.04). Reductions in periodontal inflammation were greatest in individuals with higher levels of periodontal inflammation at baseline (p=0.01) and in those with higher periodontal bone loss at baseline (p=0.03). The reductions in periodontal inflammation correlated with reductions in carotid inflammation (p<0.001).

"The impact of high-dose statin was greatest in individuals with evidence of active periodontitis and was evident after a four-week treatment period," said lead author Sharath Subramanian, MD, Massachusetts General Hospital and Harvard Medical School, Boston. "We observed a close relationship between reductions in periodontal and atherosclerotic inflammation. These results identify a potentially novel pleiotropic effect of statins and raise the possibility that an indirect benefit of statins on atherosclerosis may in part relate to a reduction in extra-arterial inflammation."

The authors note that since it was a small study, moving forward, larger, randomized studies are needed to examine the underlying mechanism of the association between localized inflammation in the periodontium and other tissues and atherosclerosis.

In an editorial comment, Michael Blaha, MD, MPH, The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, wrote, "Historically statins have been viewed as exclusively lipid-lowering medications that should be directed to patients with high serum lipid levels. A more modern perspective paints statins as cardiovascular risk-reducing medications with multiple possible mechanisms of action."

He notes that the current study "has tremendous potential implications for our philosophy toward statin allocation in primary prevention and future testing of new anti-atherosclerotic drugs."

Keywords: Inflammation, Atherosclerosis, Plaque, Atherosclerotic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Periodontitis, Risk Factors, Heptanoic Acids, Primary Prevention, Positron-Emission Tomography, Lipoproteins, LDL, Pyrroles, Cholesterol, Cardiovascular Diseases, Alveolar Bone Loss

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